Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University Bratislava, Slovak Republic.
GYN - FIV a.s., Centre for Gynaecology and Assisted Reproduction, Bratislava, Slovak Republic.
Life Sci. 2023 Nov 15;333:122179. doi: 10.1016/j.lfs.2023.122179. Epub 2023 Oct 16.
Early postnatal development can be significantly compromised by changes in factors provided by the mother, leading to increased vulnerability to hypertension in her offspring. TGR(mRen-2)27 (TGR) mothers, characterised by an overactivated renin-angiotensin system, exhibit altered ion composition in their breast milk. Therefore, we aimed to analyse the impact of cross-fostering on cardiovascular parameters in hypertensive TGR and normotensive Hannover Sprague-Dawley (HanSD) offspring.
We measured cardiovascular parameters in 5- to 10-week-old male offspring by telemetry. The expression of proteins related to vascular function was assessed by western blotting in the aortic samples obtained from 6- to 12-week-old male offspring. Plasma renin activity and plasma angiotensin II (Ang II) levels were evaluated by radioimmunoassay (RIA).
The development of hypertension was in TGR accompanied by increased low-to-high frequency ratio (LF/HF; a marker of sympathovagal balance; 0.51 ± 0.16 in week 10). Furthermore, TGR exhibited increased aortic expression of mineralocorticoid receptor (MR; p < 0.05) and transforming growth factor beta type 1 (TGF-β1; p = 0.002) compared to HanSD offspring. Fostering significantly decreased sympathovagal balance (0.23 ± 0.10 in week 10) and, transiently, plasma Ang II levels and MR expression in TGR offspring reared by HanSD mothers.
These findings highlight the importance of understanding the complex interplay between early life experiences, maternal factors, and later cardiovascular function. Understanding the mechanisms behind the observed effects may help to identify potential interventions to prevent the development of hypertension later in life.
母亲提供的因素发生变化会显著影响后代出生后的早期发育,导致其后代更容易患高血压。TGR(mRen-2)27(TGR)母亲的肾素-血管紧张素系统过度活跃,其母乳中的离子组成发生改变。因此,我们旨在分析交叉寄养对高血压 TGR 和正常血压 Hannover Sprague-Dawley(HanSD)后代心血管参数的影响。
通过遥测法测量 5-10 周龄雄性后代的心血管参数。通过 Western 印迹法评估从 6-12 周龄雄性后代获得的主动脉样本中与血管功能相关的蛋白表达。通过放射免疫分析法(RIA)评估血浆肾素活性和血管紧张素 II(Ang II)水平。
高血压的发展伴随着 TGR 中交感神经-迷走神经平衡的增加(LF/HF 比值增加,即 0.51±0.16 在第 10 周)。此外,TGR 表现出主动脉中矿皮质激素受体(MR;p<0.05)和转化生长因子-β1(TGF-β1;p=0.002)表达增加,与 HanSD 后代相比。与 HanSD 母亲抚养的 TGR 后代相比,寄养显著降低了交感神经-迷走神经平衡(0.23±0.10 在第 10 周),并短暂降低了血浆 Ang II 水平和 MR 表达。
这些发现强调了理解早期生活经历、母体因素和后期心血管功能之间复杂相互作用的重要性。了解观察到的影响背后的机制可能有助于确定潜在的干预措施,以预防以后生活中高血压的发生。